Diabetic retinopathy represents a major cause of blindness in the U.S. today. Presently, no method allows a prediction that advanced retinopathy will later develop in an individual with diabetes mellitus. There is evidence from twin and ethnic studies that genetic factors, in addition to metabolic factors, may affect the development of severe retinopathy. The proposed study will test the hypothesis that there are one or more "microangiopathy genes" in linkage dysequilibrium with HLA genes which determine susceptibility to severe diabetic retinopathy. Diabetic populations to be studied include groups of JIDD and AOD patients selected by the documented presence or absence of proliferatve retinopathy. The value of HLA antigen associations as predictors of visual outcome will be studied by an evaluation of the patients followed in the DRS and ETDRS at the University of Minnesota. In addition, diabetic multiplex families with a high prevalence of proliferative retinopathy will be studied for linkage analysis. These students will permit an evaluation of the role of HLA-related genetic markers in the development of proliferative diabetic retinopathy.